MOR-1 Expression in Colorectal Cancer and Disease-free Survival Relationship. Five-year Follow-up.

Overview

Colorectal cancer (CRC) is a global burden and one of the most frequent types of cancer. Colorectal cancer therapy is complex and surgery remains the cornerstone for its treatment, combined with chemotherapy and radiotherapy. At diagnosis time, stage II / III is the predominant . There is a growing interest on the potential effect of perioperative anesthetic management on cancer growth and spread. Preclinical studies suggest that opioids could promote direct tumor growth, angiogenesis, metastasis and immunosuppression of cellular and humoral responses, mainly mediated by Mu opioid receptor 1 (MOR-1) activation. Association between increased expression of MOR-1and or perioperative opioids use and shorter DFS or OS has been demonstrated in lung, prostate, gastric and esophagus cancers. Furthermore a pooled analysis suggested that methylnaltrexone, a peripherally acting Mu-opioid receptor antagonist (PAMORA) was associated with increased survival in patients with advanced cancer. Thus, the expression of the MOR-1 is an indicator of poor prognosis in some cancer types, but its relevance in colon cancer is unknown. The hypothesis of this study is that the increased MOR-1expression in tumor samples from colorectal cancer could be associated to poor disease free survival. These findings would be of great clinical relevance in order to avoid perioperative opioid use in oncological patients. Moreover PAMORAs could be a valuable tool in perioperative antitumor treatment, since currently these drugs are currently used with confirmed tolerability and low adverse effects in the management of opioid-induced constipation (Opioid Induced Constipation-OIC). Besides MOR 1 expression could constitute a biomarker that guide the investigators to perform neoadjuvant therapy.

PRIMARY OBJECTIVES: To evaluate the association between Mu opioid receptor 1 (MOR-1) expression in patients with colorectal cancer stage II / III submitted to scheduled curative surgery and disease-free survival (DFS) five years follow up after surgery. SECONDARY OBJECTIVES: To evaluate the association between the MOR-1 expression in patients with colorectal cancer stage II / III undergoing scheduled curative surgery and overall survival (OS) five years follow up after surgery. To evaluate the association between MOR-1 expression in patients with colorectal cancer stage II / III submitted to scheduled curative surgery and perioperative complications until postoperative day 28th after surgery. To evaluate the association between perioperative opioids dose (morphine equivalents) and disease-free survival/overall survival until five years after surgery. To evaluate MOR-1 expression differences in paraffin samples from patients with colorectal cancer stage II / III submitted scheduled colorectal surgery between the tumor tissue and the adjacent nontumorous tissue.